Clinical studies have suggested an association between increased consumption of iodine and a sharp rise in the incidence of autoimmune thyroiditis in recent years. Studies in our laboratory have shown that dietary iodine, administered from the time of hatching, markedly increases the incidence and severity of autoimmune thyroiditis in a genetically susceptible chicken strain (CS). The aim of the proposed study is to characterize this effect more fully and to investigate its mechanism. Initial experiments will determine if iodine induces as severe a disease in genetically non-susceptible chickens or in older CS chickens or in thyroid glands chronically stimulated by thyrotropin (TSH). The hypothesis that iodine exerts its effect by an action on the thyroid gland will be tested by determining the effect of iodination on the immunogenicity of thyrogloubulin (Tg) in vivo, the effect of iodine on plasma Tg concentration and iodine content and the effect of iodine on the expression of BL (class II MHC) antigens on the thyroid cell. The antigenic determinants on the Tg molecule which stimulate the spontaneous production of autoantibodies to Tg, thyroxine (T4) and triiodothyronine (T3) will be defined. Tg from strains with high, medium and low incidences of thyroiditis will be compared in relation to iodine content, antigenic determinants, immunogenicity and tolerogenicity. The possibility that iodine alters the Tg-specific and/or non-specific responses of the immune system will be investigated by in vitro and in vivo analysis of lymphocytes isolated from the thyroid gland of animals treated with various doses of iodine. The effect of iodine on antigen processing by macrophages in vitro will be determined. These studies should provide insight into the mechanism underlying the induction of autoimmune thyroid disease by iodine. They should also allow greater understanding of the genetic and environmental factors that increase the susceptibility of the population to the effects of excess dietary iodine.